Calcium silicates (monocalcium silicate CS, di-calcium silicate C2S and tri-calcium silicate C3S) are well known to hydrate and set and harden when mixed with water, through precipitation of gel-like calcium silicate hydrate (Ca—Si—H2O gel) (C—S—H), similar to ordinary Portland cement (OPC).
The open literature indicates that hydroxyapatite nuclei can form and grow on hydrated calcium silicate particles, and therefore hydrated calcium silicates are potential candidates as biomaterials for hard tissue repair (Gou, et al., “Synthesis and in vitro bioactivity of dicalcium silicate powders” Journal of the European Ceramic Society 24 (2004) 93-99). Also, Ni et al (J Biomed Mater Res Part B: Appl Biomater 80B: 174-183, 2007) investigated “Comparison of Osteoblast-Like Cell Responses to Calcium Silicate and Tricalcium Phosphate Ceramics In Vitro”. The results indicate that calcium silicate ceramics are biocompatible and bioactive and therefore suitable as new bone repair biomaterials.
Recently, certain Portland cement—based materials (referred to as mineral trioxide aggregate, MTA) have been also used for dental applications, such as endodontic dental treatment and the retention of a core (Vargas et al., “A Comparison of the In vitro Retentive Strength of Glass-Ionomer Cement, Zinc-Phosphate Cement, and Mineral Trioxide Aggregate for the Retention of Prefabricated Posts in Bovine Incisors” J. Endodont. 30(11) 2004, 775-777). MTA is a Portland cement-like material, which consists primarily of tricalcium silicate, tricalcium oxide, and tricalcium aluminates [Torabinejad et al. “Physical and chemical properties of a new root-end filling material”. J Endodont 21(1995) 349-253]. MTA has been used in many surgical and non-surgical applications, and possesses the biocompatibility and sealing abilities requisite for a perforation material (Lee, et al, “Sealing ability of a mineral trioxide aggregate for repair of lateral root perforations” J Endod 1993;19:541-4.). It can be used both as a non-absorbable barrier and restorative material for repairing root perforations. Because it is hydrophilic and requires moisture to set, MTA is the barrier of choice when there is potential for moisture contamination or when there are restrictions in technical access and visibility.
The physical and chemical properties of MTA have been tested and the initial pH on mixing was 10.2 rising to 12.5 after 3 h; it also has good compressive strength after setting. The MTA was demonstrated to be significantly less toxic than other root-end filing materials when freshly mixed, and toxicity was negligible when fully set at 24 h (Mitchell, et al, “Osteoblast biocompatibility of mineral trioxide aggregate” Biomaterials 20 (1999) 167-173)
Torabinejad et al (U.S. Pat. No. 5,415,547, U.S. Pat. No. 5,769,638) disclosed an improved method for filing and sealing tooth cavities, which involves the use of an MTA cement composition, including the ability to set in an aqueous environment. The cement composition comprises Portland cement, or variations in the composition of such cement, which exhibit favorable physical attributes sufficient to form an effective seal against re-entrance of infectious organisms. However, the cement is gray in color, which is unsuitable for many dental applications.
Primus (US Patent Appl. No. 2003/0159618) disclosed a process for making a white, substantially non-iron containing dental material based on a Portland cement composition. The material may be used as a dental cement, dental restorative or the like. However, this process only decreased the iron content but did not improve biological properties of these materials.
LU et al (PCT/CA2006/001761) disclosed a composition of hydraulic cement for medical applications comprising calcium silicates and phosphates, referred to as Calcium Phosphate Silicate Cement (CPSC), which employs in-situ setting and hardening. The composition is claimed to be suitable for dental, implants, bone fixation, and bone repair applications. The CPSC has high mechanical strength, adjustable setting time, low hydration heat, resistance to bio-degradation, high bioactivity and biocompatibility, and stability against corrosive environments. The cement employs a novel chemical process of in-situ formation of hydroxyapatite/calcium silicate hydrate gel composite at room- or nearly room-temperature and pressure, accompanied by the removal of calcium hydroxide Ca(OH)2, referred to as CH, during cement hydration. This is accomplished through in-situ reacting the CH with phosphate ions to precipitate much stronger and chemically resistant calcium phosphate, in particular hydroxyapatite (HAP), intimately mixed with the C—S—H gel resulting from hydration of calcium silicates. As a result of this in-situ chemical precipitation process the composite cement has high mechanical strength, but also biocompatibility, bioactivity, and adjustable setting time. These properties do not require application of hydrothermal treatment or pressure-assisted forming of the components. However, like the MTA and Calcium Phosphate Cement (CPC) described above, the CPSC powder must be mixed with water to initiate the hydration and setting process.
Mixing and handling of cements is a key aspect of any particular application. For clinical uses, it is very important to properly mix the cement with liquid, such as water, and then place the cement paste in the defect within the prescribed time, which is a crucial factor in achieving optimum results. One of the main issues related to the mixing process is insufficient and inhomogeneous mixing of solids with liquids, or improper ratio of cement solids to water, thus compromising the implant placement, setting process, set properties, and thus performance. It is therefore desirable that cements be premixed under well-controlled conditions; premixing is widely practiced in construction, e.g., premixed concrete delivered in trucks, however, hydraulic cements premixed with water have rather short working time and must be delivered to the application site immediately. Another issue, specific to medical cements, is that all the individual components of the cement material and the equipment need to be sterilized, and the mixing needs to be performed in a sterile environment. Also, mixing time may understandably increase the total surgical placement time. Thus, it would be desirable to have a premixed cement paste that is stable in the sterile package for extended period of time, that is easy to implant after the package is opened, and that hardens only after being placed in the defect.
Takagi, et al (J Biomed Mater Res Part B: Appl Biomater 67B: 689-696, 2003) reported the results of research involving Premixed Calcium Phosphate Cement (CPC) pastes. The premixed pastes were prepared by mixing water-free glycerol and calcium phosphate cement powder to form a stable paste. The calcium phosphate cement hardened only after being delivered to a defect site where glycerol-tissue fluids exchange occurred. However, set calcium phosphate cement is biodegradable and has relatively low mechanical strength, and therefore is not suitable for many medical or dental applications. (Xu, et al, “Premixed calcium phosphate cements:Synthesis, physical properties, and cell cytotoxicity” dental materials 23 (2007) 433-441).